Healthy bones continuously undergo a remodeling process, where an equilibrium is reached between bone resorption and bone formation through the concerted action of active bone cells, i.e. bone forming osteoblasts and bone resorbing osteoclasts. The bone remodeling process begins with activation of cells covering unmineralized bone, i.e. lining cells. The lining cells resorb the unmineralized bone, then retract and leave room for the osteoclasts which resorb the old, mineralized bone and create an environment which attracts the osteoblast to the same site. The osteoblasts thereafter lay down an organic matrix, which subsequently becomes mineralized to form new bone. Thus bone mass is determined by the balance between bone resorption by osteoclasts and bone formation by osteoblasts.
The amount of mineral in bone is largely responsible for its hardness, while substances like the structural protein collagen also contribute to bone's mechanical strength. The dense outermost bone is known as cortical bone while the more spongy internal form is known as cancellous or trabecular bone.
Most bone diseases are due to a disruption in the equilibrium of the bone remodeling process. Generally, the disruption is an increase in bone resorption. For example, osteoporosis, one of the most common bone diseases, is characterized by a decrease in bone mass along with a microstructural change in bone, but there is no effect on the chemical composition of bone itself which results in increased susceptibility to bone fractures. Specifically, the cortical bone becomes thin and porous while the trabecular bone becomes thinned, perforated, and disconnected. Osteoporosis may be considered the result of a negative balance in the bone remodeling cycle, i.e. less bone is formed than is being resorbed.
Thus, therapeutic agents for treating bone disorders are directed at inhibiting bone resorption and increasing bone formation. There are many different molecules and pathways involved in the bone remodeling process and the various therapeutic agents presently available target different molecules and pathways. For example, bisphosphonates (such as aledronate and risedronate) inhibit bone resorption by blocking osteoclast activity. Other therapeutic agents seek to inhibit bone resorption by blocking binding to members of the TNF receptor/ligand family, such as Receptor Activator for Nuclear Factor κB Ligand (RANK-L), a cytokine that activates osteoclasts, the cells that are involved in bone resorption. Inhibition of release of RANK-L prevents bone mineral loss.
Still other therapeutic agents target increasing bone formation. For example, activated bone morphogenic protein gene is known to have direct effects on triggering osteoblast cell differentiation and promoting bone formation. Delivery of recombinant bone morphogenic protein-2 (BMP-2) has been shown to induce bone or cartilage formation. However, systemic administration of pharmaceutical and biological agents, such as recombinant BMP-2, can have deleterious effects on the intestine and other tissues. Therefore, there is a need in the art for natural and plant-derived extracts, that can be used in dietary supplement interventions for preventing and/or treating bone disorders by inhibiting bone resorption and/or increasing bone formation.